Cigarette smoking remains the single most preventable cause of mortality and morbidity in the United States. Long-term abstinence rates for even the most rigorous of smoking cessation treatments range between 20 percent and 35 percent. It is therefore essential that research continue to investigate novel smoking cessation interventions. Considerable evidence suggests that withdrawal processes form the motivational basis for cigarette smoking and play a critical role in relapse to cigarette use. While withdrawal from nicotine, or pharmacologic withdrawal, may be limited to 10 days, withdrawal from the act of smoking, or behavioral withdrawal, may persist indefinitely. Accordingly, it has been suggested that smoking cessation interventions may be augmented by aiding smokers in the practice of withdrawal regulation strategies. The primary goal of this investigation is to pilot an in vivo early withdrawal exposure with withdrawal regulation training intervention for smoking cessation. Specific aims include: informing the feasibility of investigating the experimental intervention;determining the experimental treatment's potential efficacy;and investigating mediators and moderators of the experimental treatment. Participants will be adult smokers (N = 50) of at least 10 cigarettes per day with the intention to quit smoking. They will be randomized to one of two conditions: Early Withdrawal Exposure + Withdrawal Regulation Training (E + WT) or Relaxation Training control (RT). The E + WT condition will consist of the development, application, modification, and repeated practice of individualized withdrawal regulation strategies (e.g., behavioral and cognitive strategies for allaying withdrawal symptoms) over three separate sessions that will each span the first four hours of abstinence. The RT condition will control for the therapeutic contact received by those in the E + WT condition. While the proposed investigation is expected to prove feasible, the proposed pilot study will provide an array of data critical to the advancement of the study design, recruitment and retention strategies, and treatment protocol, which includes the treatment manuals. Furthermore, outcome data will allow for the refinement of effect size estimates of the experimental intervention. Finally, candidate mediators (e.g., withdrawal symptoms) and moderators (e.g., tobacco dependence) will be investigated via established analyses. These data will advance the experimental intervention with a focus on targeting mechanisms of change as well as participant characteristics to which the intervention may be tailored. The experimental intervention described in the current application has the potential to ultimately enhance the efficacy of existing smoking cessation interventions and will therefore contribute uniquely to the field. PUBLIC HEALTH RELEVANCE: Smoking remains the single most preventable cause of morbidity and mortality in the United States, accounting for approximately half a million deaths every year. The current study will investigate the feasibility, potential efficacy, and mechanisms of change of a novel smoking cessation intervention. The current study will thus provide essential information regarding a treatment that has the potential to enhance the efficacy of existing smoking cessation interventions, thereby having a beneficial impact on the public health of the United States.